Quarky Calcium Release in the HeartNovelty and Significance
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Rationale: In cardiac myocytes, “Ca2+ sparks” represent the stereotyped elemental unit of Ca2+ release arising from activation of large arrays of ryanodine receptors (RyRs), whereas “Ca2+ blinks” represent the reciprocal Ca2+ depletion signal produced in the terminal cisterns of the junctional sarcoplasmic reticulum. Emerging evidence, however, suggests possible substructures in local Ca2+ release events.
Objective: With improved detection ability and sensitivity provided by simultaneous spark–blink pair measurements, we investigated possible release events that are smaller than sparks and their interplay with regular sparks.
Methods and Results: We directly visualized small solitary release events amid noise: spontaneous Ca2+ quark-like or “quarky” Ca2+ release (QCR) events in rabbit ventricular myocytes. Because the frequency of QCR events in paced myocytes is much higher than the frequency of Ca2+ sparks, the total Ca2+ leak attributable to the small QCR events is approximately equal to that of the spontaneous Ca2+ sparks. Furthermore, the Ca2+ release underlying a spark consists of an initial high-flux stereotypical release component and a low-flux highly variable QCR component. The QCR part of the spark, but not the initial release, is sensitive to cytosolic Ca2+ buffering by EGTA, suggesting that the QCR component is attributable to a Ca2+-induced Ca2+ release mechanism. Experimental evidence, together with modeling, suggests that QCR events may depend on the opening of rogue RyR2s (or small cluster of RyR2s).
Conclusions: QCR events play an important role in shaping elemental Ca2+ release characteristics and the nonspark QCR events contribute to “invisible” Ca2+ leak in health and disease.
- Received June 4, 2009.
- Revision received January 17, 2010.
- Revision received November 17, 2010.
- Accepted November 30, 2010.
- © 2011 American Heart Association, Inc.